Hydrocortisone

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Hydrocortisone
Cortisol3.svg
Cortisol-3D-balls.png
Clinical data
Trade names A-hydrocort, Cortef, Solu-cortef, others [1]
Other namesCortisol; 11β,17α,21-Trihydroxypregn-4-ene-3,20-dione; 11β,17α,21-Trihydroxyprogesterone
AHFS/Drugs.com Monograph
MedlinePlus a682206
License data
Pregnancy
category
Routes of
administration 		By mouth (tablets), intravenous, topical, rectal
Drug class Corticosteroid; Glucocorticoid; Mineralocorticoid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Oral: 96 ± 20% [11] [12]
Protein binding 92 ± 2% (92–93%) [11] [12]
Metabolism 11β-HSDs Tooltip 11β-Hydroxysteroid dehydrogenases, others [12]
Metabolites Cortisone, others [12]
Onset of action Oral: 1.2 ± 0.4 hours (Tmax) [11]
Elimination half-life 1.2–2.0 hours [11] [12]
Duration of action 8–12 hours [13]
Identifiers
  • (8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C21H30O5
Molar mass 362.466 g·mol−1
3D model (JSmol)
  • O=C4\C=C2/[C@]([C@H]1[C@@H](O)C[C@@]3([C@@](O)(C(=O)CO)CC[C@H]3[C@@H]1CC2)C)(C)CC4
  • InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1 Yes check.svgY
  • Key:JYGXADMDTFJGBT-VWUMJDOOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Hydrocortisone is the name for the hormone cortisol when supplied as a medication. [14] Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD. [1] It is the treatment of choice for adrenocortical insufficiency. [15] It can be given by mouth, topically, or by injection. [1] Stopping treatment after long-term use should be done slowly. [1]

Contents

Side effects may include mood changes, increased risk of infection, and edema (swelling). [1] With long-term use common side effects include osteoporosis, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections). [1] It is unclear if it is safe for use during pregnancy. [16] Hydrocortisone is a glucocorticoid and works as an anti-inflammatory and by immune suppression. [1]

Hydrocortisone was patented in 1936 and approved for medical use in 1941. [17] [18] It is on the World Health Organization's List of Essential Medicines. [19] It is available as a generic medication. [1] In 2020, it was the 149th most commonly prescribed medication in the United States, with more than 3 million prescriptions. [20] [21]

Medical uses

Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an adrenal crisis. It may also be injected into inflamed joints resulting from diseases such as gout.

It may be used topically for allergic rashes, eczema, psoriasis, itching and other inflammatory skin conditions. Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only.[ citation needed ]

It may also be used rectally in suppositories to relieve the swelling, itch, and irritation in haemorrhoids. [7]

It may be used as an acetate form (hydrocortisone acetate), which has slightly different pharmacokinetics and pharmacodynamics. [7] [22]

Pharmacology

Pharmacodynamics

Hydrocortisone is a corticosteroid, acting specifically as both a glucocorticoid and as a mineralocorticoid. That is, it is an agonist of the glucocorticoid and mineralocorticoid receptors.

Hydrocortisone has low potency relative to synthetic corticosteroids. [13] Compared to hydrocortisone, prednisolone is about 4 times as potent and dexamethasone about 40 times as potent in terms of anti-inflammatory effect. [23] Prednisolone can also be used as cortisol replacement, and at replacement dose levels (rather than anti-inflammatory levels), prednisolone is about 8 times more potent than cortisol. [24] The equivalent doses and relative potencies of hydrocortisone compared to various other synthetic corticosteroids have also been reviewed and summarized. [13]

The endogenous production rate of cortisol is approximately 5.7 to 9.9 mg/m2 per day, which corresponds to an oral hydrocortisone dose of approximately 15 to 20 mg/day (for a 70-kg person). [25] [26] One review described daily cortisol production of 10 mg in healthy volunteers and reported that daily cortisol production could increase up to 400 mg in conditions of severe stress (e.g., surgery). [11]

The total and/or free concentrations of cortisol/hydrocortisone required for various glucocorticoid effects have been determined. [11]

Pharmacokinetics

Absorption

The bioavailability of oral hydrocortisone is about 96% ± 20% (SD). [11] [12] The pharmacokinetics of hydrocortisone are non-linear. [11] The peak level of oral hydrocortisone is 15.3 ± 2.9 (SD) μg/L per 1 mg dose. [11] The time to peak concentrations of oral hydrocortisone is 1.2 ± 0.4 (SD) hours. [11]

The topical percutaneous absorption of hydrocortisone varies widely depending on experimental circumstances and has been reported to range from 0.5 to 14.9% in different studies. [27] Some skin application sites, like the scrotum and vulva, absorb hydrocortisone much more efficiently than other application sites, like the forearm. [27] [28] [29] In one study, the amount of hydrocortisone absorbed ranged from 0.2% to 36.2% depending on the application site, with the ball of the foot having the lowest absorption and the scrotum having the highest absorption. [29] The absorption of hydrocortisone by the vulva has ranged from 4.4 to 8.1%, relative to 1.3 to 2.8% for the arm, in different studies and subjects. [29] [30] [31]

Distribution

Most cortisol in the blood (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and serum albumin. A pharmacokinetic review stated that 92% ± 2% (SD) (92–93%) of hydrocortisone is plasma protein-bound. [11] Free cortisol passes easily through cellular membranes. [32] Inside cells it interacts with corticosteroid receptors. [33]

Metabolism

Hydrocortisone is metabolized by 11β-hydroxysteroid dehydrogenases (11β-HSDs) into cortisone, an inactive metabolite. [12] [11] It is additionally 5α-, 5β-, and 3α-reduced into dihydrocortisols, dihydrocortisones, tetrahydrocortisols, and tetrahydrocortisones. [34] [11] [12]

Elimination

The elimination half-life of hydrocortisone ranges from about 1.2 to 2.0 (SD) hours, with an average of around 1.5 hours, regardless of oral versus parenteral administration. [11] [12] The duration of action of systemic hydrocortisone has been listed as 8 to 12 hours. [13]

Chemistry

Hydrocortisone, also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a naturally occurring pregnane steroid. [35] [36] A variety of hydrocortisone esters exist and have been marketed for medical use. [35] [36]

Society and culture

On 25 March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Efmody, intended for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older. [37] The applicant for this medicinal product is Diurnal Europe BV. [37] Hydrocortisone (Efmody) was approved for medical use in the European Union, in May 2021, for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older. [9]

Anti-competitive practices

In the UK, the Competition and Markets Authority (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and Actavis plc had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "generic" rather than branded products and thereby escape price controls until eventually other companies entered the market. Auden and Actavis overcharged the UK's National Health Service for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of competition law. [38]

Research

COVID-19

Hydrocortisone was found to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo. [39]

Related Research Articles

<span class="mw-page-title-main">Corticosteroid</span> Class of steroid hormones

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

<span class="mw-page-title-main">Cushing's syndrome</span> Symptoms from excessive exposure to glucocorticoids such as cortisol

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

<span class="mw-page-title-main">Cortisone</span> Corticosteroid precursor and metabolite of cortisol

Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase isozyme 2 into the inactive metabolite cortisone, particularly in the kidneys. This is done by oxidizing the alcohol group at carbon 11. Cortisone is converted back to the active steroid cortisol by stereospecific hydrogenation at carbon 11 by the enzyme 11β-Hydroxysteroid dehydrogenase type 1, particularly in the liver.

<span class="mw-page-title-main">Dexamethasone</span> Corticosteroid medication

Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cava syndrome, and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone. In preterm labor, it may be used to improve outcomes in the baby. It may be given by mouth, as an injection into a muscle, as an injection into a vein, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye. The effects of dexamethasone are frequently seen within a day and last for about three days.

<span class="mw-page-title-main">Addison's disease</span> Endocrine disorder

Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal glands, causing adrenal insufficiency. Symptoms generally come on slowly and insidiously and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss. Darkening of the skin in certain areas may also occur. Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure, which is a clinical emergency. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.

<span class="mw-page-title-main">Prednisone</span> Steroid medication

Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids. It is taken by mouth.

<span class="mw-page-title-main">Glucocorticoid</span> Class of corticosteroids

Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure.

<span class="mw-page-title-main">Adrenal insufficiency</span> Medical condition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

<span class="mw-page-title-main">Prednisolone</span> Chemical compound (steroid medication)

Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthritis, dermatitis, eye inflammation, asthma, and multiple sclerosis. It can be taken by mouth, injected into a vein, used topically as a skin cream, or as eye drops. It differs from the similarly named prednisone in having a hydroxyl at the 11th carbon instead of a ketone.

<span class="mw-page-title-main">Fludrocortisone</span> Mineralocorticoid Hormone used as a Medicine

Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydrocortisone. Fludrocortisone is taken by mouth and is most commonly used in its acetate form.

<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.

<span class="mw-page-title-main">Methylprednisolone</span> Corticosteroid medication

Methylprednisolone is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.

<span class="mw-page-title-main">Hydrocortisone acetate</span> Chemical compound

Hydrocortisone acetate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester.

<span class="mw-page-title-main">Aminoglutethimide</span> Group of stereoisomers

Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. It has also been used by bodybuilders, athletes, and other men for muscle-building and performance- and physique-enhancing purposes. AG is taken by mouth three or four times per day.

<span class="mw-page-title-main">Loteprednol</span> Pharmaceutical drug

Loteprednol is a topical corticosteroid used to treat inflammations of the eye. It is marketed by Bausch and Lomb as Lotemax and Loterex.

<span class="mw-page-title-main">Adrenal crisis</span> Medical condition

Adrenal crisis, also known as Addisonian crisis or Acute adrenal insufficiency, is a serious, life-threatening complication of adrenal insufficiency. Hypotension, or hypovolemic shock, is the main symptom of adrenal crisis, other indications and symptoms include weakness, anorexia, nausea, vomiting, fever, fatigue, abnormal electrolytes, confusion, and coma. Laboratory testing may detect lymphocytosis, eosinophilia, hyponatremia, hyperkalemia, hypoglycemia, and on occasion, hypercalcemia.

Critical illness–related corticosteroid insufficiency is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.

<span class="mw-page-title-main">Vamorolone</span> Chemical compound

Vamorolone, sold under the brand name Agamree, is a synthetic corticosteroid, which is used for the treatment of Duchenne muscular dystrophy. It is taken by mouth.

<span class="mw-page-title-main">Topical glucocorticoids</span>

Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory, antimitotic, and immune-system suppressing actions through various mechanisms.

<span class="mw-page-title-main">Topical hydrocortisone</span> Pharmaceutical drug

Topical hydrocortisone is a drug under the class of corticosteroids, which is used for the treatment of skin inflammation, itchiness and allergies. Some examples include insect bites, dermatitis and rash.

References

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  2. ↑ "Prescribing medicines in pregnancy database". Therapeutic Goods Administration (TGA). Retrieved 21 February 2021.
  3. ↑ "Hydrocortisone Notice of enforcement policy" (PDF). FDA. Retrieved 31 December 2022.
  4. ↑ "Ala-cort- hydrocortisone cream". DailyMed. Retrieved 21 February 2021.
  5. ↑ "Ala-scalp- hydrocortisone lotion". DailyMed. Retrieved 21 February 2021.
  6. ↑ "Alkindi Sprinkle- hydrocortisone granule". DailyMed. Retrieved 21 February 2021.
  7. 1 2 3 "Anusol HC- hydrocortisone acetate suppository". DailyMed. Retrieved 21 February 2021.
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  9. 1 2 "Efmody EPAR". European Medicines Agency (EMA). 24 March 2021. Retrieved 14 June 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. ↑ "Efmody Product information". Union Register of medicinal products. Retrieved 3 March 2023.
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  17. ↑ U.S. patent 2,183,589
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  37. 1 2 "Efmody: Pending EC decision". European Medicines Agency (EMA). 25 March 2021. Archived from the original on 4 May 2021. Retrieved 27 March 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  38. ↑ UKOpenGovernmentLicence.svg  This article incorporates text published under the British Open Government Licence : Competition and Markets Authority, Decision: Hydrocortisone tablets. Excessive and unfair pricing and Anti-competitive agreements , published 31 March 2022, accessed 1 June 2023
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